Abstract WP155: Delayed Administration of Angiotensin Receptor (AT2-R) Agonist C21 Downregulates Diabetes Induced Pro-Inflammatory Microglia Activation Post-Stroke in Female Rats: Therapeutic Indications for Vascular Cognitive Impairment & Dementia
Bibliographic record
Abstract
Post-stroke cognitive impairment (PSCI) occurs in up to 48% of patients, for which there is no therapy. Although 70% of stroke victims present with comorbid diseases such as diabetes and hypertension, the inadequate integration of these comorbidities into experimental studies limited our understanding of the mechanisms involved in the development of PSCI. Based on our recent findings that 1) the increased prevalence of PSCI in male diabetic animals is linked to heightened chronic inflammation and 2) even delayed administration of compound 21 (C21), an angiotensin II Type 2 receptor agonist, effectively reduces PSCI by lowering inflammation in male animals, we hypothesized that a delayed administration of C21 would also lower chronic inflammation post-stroke in female animals. Methods: Diabetes was induced by a high fat diet (HFD) and low dose streptozotocin (STZ) combination. Rats were subjected to 1 h middle cerebral artery occlusion (MCAO) or sham surgery. 3 days post-stroke, rats were administered C21 or vehicle in drinking water at a dose of 0.12 mg/kg/day for 4 weeks. The direct effect of C21 on microglia polarization was determined in mouse cells (C8B4) and the mature:pro BDNF ratio was evaluated through western blot. Samples from freshly harvested brains (B-D slice containing the prefrontal cortex through the hippocampus), and from cell culture were analyzed by flow cytometry. Results: Delayed administration of C21 starting 3 days post-stroke improved inflammation through modulation of the M1/M2 ratio. Cell culture results indicated that along with decreasing the M1/M2 ratio, it also increased the mature/pro-BDNF ratio. Conclusion: Delayed administration of C21 downregulates post-stroke inflammation in both male and female diabetic animals. This study emphasizes the importance of translational disease modeling and suggests that C21 may be a useful therapeutic option to lower inflammation and prevent PSCI in comorbid diseases.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".